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Patent Issued for Antifouling Hydrogels, Coatings, and Methods of Synthesis and Use

August 19, 2014



By a News Reporter-Staff News Editor at Life Science Weekly -- According to news reporting originating from Alexandria, Virginia, by NewsRx journalists, a patent by the inventors Messersmith, Phillip B. (Clarendon Hills, IL); Rivera, Jose (Waukegan, IL); Gong, Yong-Kuang (Xian, CN), filed on August 26, 2010, was published online on August 5, 2014 (see also Northwestern University).

The assignee for this patent, patent number 8796394, is Northwestern University (Evanston, IL).

Reporters obtained the following quote from the background information supplied by the inventors: "Preventing the non-specific protein adsorption and cell adhesion on biosensors, biomedical devices, and implants is crucial for the performance of these devices..sup.1,2 Many strategies to prevent such non-specific protein adsorption and cell adhesion have been developed. For instance, a variety of polymers have been used to reduce protein, cell and bacterial adsorption at interfaces with biological tissues. Of these, poly(ethylene glycol) (PEG) is one of the most promising synthetic polymers to confer protein and cell resistance to devices having PEG immobilized onto the surface..sup.3

"Although ethylene glycol may be block-copolymerized with other hydrophobic polymers to enable surface immobilization of PEG via adsorption of the hydrophobic copolymer blocks,.sup.4-6 a covalent attachment to the substrate is preferable for long term stability of PEG surface coatings. For that reason, a number of strategies have been developed to immobilize PEG onto the surfaces of biomaterials. The most frequently employed techniques are surface graft, including 'graft to' and 'graft from' methods. Thiol-terminated PEG self-assembly on gold.sup.7-12 and PEG-silane reaction on the surfaces of indium tin oxide, silica and silicon.sup.13-17 are typical 'graft to' techniques. Polymerizable PEG monoacrylates are often employed to graft and polymerize from a surface with immobilized initiators..sup.18-24 PEG-bearing amine groups were also coupled with poly(N-hydroxysuccinimidyl methacrylate) films, hydrolyzed poly(methyl methacrylate) or silanized glass slides bearing aldehyde groups, respectively..sup.14, 25-29 Polyethylene glycols containing alkyne and cyclodiene terminal groups have also been grafted onto a N-(e-maleimidocaproyl) functionalized glass slides via an aqueous Diels-Alder reaction..sup.30 Bonding of PEG-biotin derivatives onto an avidin surface was performed,.sup.31,32 and isocyanate-terminated star PEG was employed for preparing ultrathin coatings..sup.1, 33-36 PEG-bearing photoreactive groups have also been immobilized on surfaces by photocrosslinking..sup.37

"Each of these strategies require the presence of specific surface functional groups and extensive optimization of the surface. Therefore, developing a versatile immobilization strategy that is capable of robustly anchoring polymers onto a variety of material surfaces is extremely important for biomedical and other bio-related applications. For this purpose, the inventors has reported extensively on the adhesive characteristics of 3,4-dihydroxyphenylalanine (DOPA), an important component of mussel adhesive proteins, to anchor PEG and peptides on a wide number of substrates, including noble metals, semiconductors, metal oxides, synthetic polymers, ceramics and composites surfaces..sup.38-46

"The surface coverage and film thickness are two of the most important parameters influencing the antifouling performance of a PEG-coated surface. Groll and Gasteier et. al..sup.1,33,34 reported that PEG films with thicknesses between 3 and 10 nm were not able to prevent non-specific cell adhesion under standard cell culture conditions (10% fetal calf serum). However, thicker star-shaped PEG films (15-50 nm) were able to prevent cellular adhesion under the same conditions. In addition, such films did not induce thrombocyte adhesion and exhibited very good hemocompatibility. In general, conventional antifouling coatings applied in thicknesses ranging from 15-50 nm are effective at reducing the attractive interactions between fouling species (cells/proteins/bacteria) and the underlying substrate.

"Star-shaped PEG polymers have been previously employed for the preparation of hydrogel coatings through complicated methods involving substrate surface modification and polymer cross-linking by irradiation,.sup.47-51 or via reaction between the functionalized end-groups of the PEG stars..sup.35, 52-54 In this invention, we describe a facile strategy to prepare PEG nano-hydrogel coatings with tunable thickness for antifouling applications. The polymer building block is comprised of four-armed PEGs modified with dihydroxyhydrocinnamic acid (DOHA). This catechol-containing molecule has a similar molecular structure as DOPA, and it shares the same adhesive characteristics. Despite employing a polymer composition that has been shown to be adhesive to biological constituents, a surprising and unexpected outcome was obtained in which hydrogel coatings derived from DOHA-derivatized PEG were actually an effective antifouling agent for proteins, cells and bacteria when applied to various surfaces.

"Although the hydrogel coatings known from the existing art decrease cell and protein adsorption on surface to varying degrees, complex manufacturing methods for these coatings in many cases prevent wide usability. For example, conventional techniques require the use of reactive, costly, difficult to synthesize and handle coating materials; they require the use of costly irradiation units, or complicated adhesion promoters; and/or they require laborious coating processes.

"Accordingly, a need exists for an antifouling hydrogel coating that can be anchored in stably covalent fashion onto multiple substrate surfaces and can be obtained in simple fashion. A need also exists to improve the manufacturing process of such hydrogel coatings, such that, in particular, the use of adhesion promoters can be dispensed with and coatings of long-term stability are nevertheless obtained. Such a hydrogel coating and methods of synthesis and use thereof would substantially simplify the coating process and open up a broad spectrum of applications, and is not known in the existing art."

In addition to obtaining background information on this patent, NewsRx editors also obtained the inventors' summary information for this patent: "The invention provides an antifouling hydrogel comprising an effective amount of antifouling polymer modified with a compound containing catechol functional groups to yield a modified antifouling polymer comprising at least one catechol functional end group; and an effective amount of at least one oxidizing reagent, wherein the at least one oxidizing reagent reacts with the modified antifouling polymer to provide a modified antifouling polymer comprising at least one oxidized catechol end group, wherein an antifouling hydrogel is provided.

"In one embodiment, the modified polymer comprises at least two catechol end groups, although in other embodiments three, four or more catechol end groups are shown. For instance, in one embodiment, the modified antifouling polymer has a structure according to Formula I:

"##STR00001##

"In some embodiments, the at least one oxidizing reagent is selected from the group consisting of periodates, peroxides, permanganate, biological enzymes and peroxidases. For instance, in one embodiment, the at least one oxidizing reagent is silver nitrate, while in other embodiments the at least one oxidizing reagent is NaIO.sub.4. In other embodiments, the oxidizing reagent comprises silver nitrate and NaIO.sub.4 in a 4:1 ethanol:water solution.

"The invention also provides a method of synthesizing an antifouling hydrogel comprising the steps of modifying an effective amount of an antifouling polymer with an effective amount of a compound comprising at least two catechol functional groups to yield a modified antifouling polymer comprising at least two catechol end groups; and reacting the modified antifouling polymer with at least one oxidizing agent to yield a hydrogel comprising at least two oxidized catechol-end groups; thereby providing an antifouling hydrogel.

"In one embodiment, the modified antifouling polymer has a structure according to Formula I:

"##STR00002##

"In some embodiments, the at least one oxidizing reagent is selected from the group consisting of periodates, peroxides, permanganate, biological enzymes and peroxidases. For instance, in one embodiment, the at least one oxidizing reagent is silver nitrate, while in other embodiments the at least one oxidizing reagent is NaIO.sub.4. In other embodiments, the oxidizing reagent comprises silver nitrate and NaIO.sub.4 in a 4:1 ethanol:water solution.

"The invention also provides a method of synthesizing an antifouling hydrogel comprising the steps of reacting an effective amount of PEG with an effective amount of DOHA to yield a modified PEG having a structure according to Formula I:

"##STR00003## reacting an effective amount of Formula I with an effective amount of silver nitrate and NaIO.sub.4 in a 4:1 ethanol:water solution to provide a modified Formula I comprising oxidized catechol-end groups; and coating the modified Formula I comprising oxidized catechol-end groups to a surface, thereby yielding an antifouling hydrogel.

"In other embodiments, the invention provides a method of reducing or eliminating protein or microorganism adhesion on a surface, the method comprising the steps of contacting a portion of a surface with an antifouling hydrogel according to the present invention, wherein the contacted surface thereby reduces or eliminates protein or cell adhesion on the contacted surface.

"In other embodiments, the invention provides a method of reducing or eliminating protein or microorganism adhesion on a surface, the method comprising the steps of contacting a portion of a surface with an effective amount of antifouling polymer to provide an adsorbed polymer layer on the surface; contacting a portion of the adsorbed polymer layer on the surface with an effective amount of an antifouling hydrogel according to the present invention, wherein the contacted surface thereby reduces or eliminates protein or cell adhesion on the contacted surface.

"The invention also provides a kit comprising the hydrogel according to the present invention and instructions for use. In other embodiments, the kit comprises an antifouling polymer, a compound containing at least two catechol functional groups, an oxidizing reagent and instructions for use.

"While multiple embodiments are disclosed, still other embodiments of the present invention will become apparent to those skilled in the art from the following detailed description. As will be apparent, the invention is capable of modifications in various obvious aspects, all without departing from the spirit and scope of the present invention. Accordingly, the detailed descriptions are to be regarded as illustrative in nature and not restrictive."

For more information, see this patent: Messersmith, Phillip B.; Rivera, Jose; Gong, Yong-Kuang. Antifouling Hydrogels, Coatings, and Methods of Synthesis and Use. U.S. Patent Number 8796394, filed August 26, 2010, and published online on August 5, 2014. Patent URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=8796394.PN.&OS=PN/8796394RS=PN/8796394

Keywords for this news article include: Alcohols, Hydrogel, Chemistry, Silver Nitrate, Silver Compounds, Organic Chemicals, Polyethylene Glycols, Northwestern University.

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Source: Life Science Weekly


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